Hyperbilirubinemia is is probably the most frequently diagnosed and treated condition in the human newborn. Treatment attempts to prevent the entry of bilirubin into the brain, because bilirubin in neurotoxic. The mode by which bilirubin enters the neonatal brain in unknown. We demonstrated that albumin-bound bilirubin enters the brain of experimental animals, following opening of the blood-brain barrier. Since bilirubin entered only the treated hemisphere, the contralateral hemisphere serves as a control within the same animal. Then, utilizing direct carotid arterial infusion of bilirubin, we increased the content of brain bilirubin by about ten-fold. This will permit studies of the effects of bilirubin on cerebral metabolism and may provide a model of neonatal kernicterus.